ANTIHYPERTENSIVE THERAPY AND ADAPTIVE-MECHANISMS IN PERIPHERAL ISCHEMIA

In the present experiments the effect of long-term peripheral ischemia on the capillarity of two hind limb skeletal muscles was investigated in spontaneously hypertensive rats. Furthermore, the effect of antihy pertensive therapy on changes in capillarity and on the previously obs erved hyperreactivity of the ischemic vascular bed to vasoconstrictors was investigated in perfused hind limbs of rats after long-term treat ment with the angiotensin I converting enzyme inhibitors captopril (0. 5 mg/kg . h) or zabiciprilate (0.025 mg/kg . h), the angiotensin II ty pe 1 receptor antagonist losartan (0.625 mg/kg . h), or the calcium an tagonist felodipine (0.042 or 0.42 mg/kg . h). Skeletal muscle ischemi a in the left hind limb was induced by partial ligation of the left co mmon iliac artery. Long-term (4 weeks) ischemia increased significantl y the capillary-to-fiber ratio in the soleus muscle, composed predomin antly or type I fibers in spontaneously hypertensive rats, of the isch emic hind limb, whereas capillarity in the contralateral muscle was no t affected. Furthermore, capillarity in the gastrocnemius muscle (type II muscle fiber part) of both the ischemic and contralateral hind lim b did not change. Long-term treatment with the angiotensin I convertin g enzyme inhibitors during ischemia abolished the increase in the capi llary-to-fiber ratio in the soleus muscle, whereas a comparable antihy pertensive dose of felodipine had no effect. Greater blood pressure re ductions by both losartan and felodipine prevented increases in capill arization in skeletal muscle ischemia. With respect to vascular hyperr eactivity during ischemia, only treatment with losartan normalized rea ctivity of the ischemic vascular bed to vasoconstrictors. These data s uggest that both the renin-angiotensin system, probably through the an giotensin II type 1 receptor, and hypoperfusion play a role in the ada ptation mechanisms after ischemia of skeletal muscle.